Academic literature on the topic 'Genetic disorders Victoria'

Abstract Background: Neurodegeneration with Brain Iron Accumulation (NBIA) is a group of rare genetic disorders characterized by progressive degenerative motor symptoms and the accumulation of iron in the basal ganglia. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of NBIA caused by a mutation in the PANK2 gene leading to a deficiency in pantothenate kinase. Phospholipase A2G6-Associated Neurodegeneration (PLAN) is caused by a mutation in the PLA2G6 gene resulting in impaired phospholipase activity. Current understanding of systemic changes in NBIA disorders is limited, leaving no clear diagnostic biomarkers. Monitoring the systemic changes could identify candidate biomarkers for assessing disease severity and evaluating the efficacy of new therapies. Previous studies of Parkinson's disease (PD) have found a systemic burden of increased oxidative stress and chronic inflammation accompanies the neurological symptoms of the disease. Similarly, abnormal systemic iron regulation associated with brain iron accumulation as well as damage associated with neuromuscular degeneration could lead to increased oxidative stress and a state of chronic inflammation in NBIA. Our initial investigation of a patient with PLAN1, revealed elevated levels of systemic oxidative stress. We investigated a group of PKAN patients as well as continued our investigation of a patient with PLAN to evaluate the possibility of abnormal iron trafficking, increased oxidative stress and chronic inflammation in NBIA. Our aim was to expand our investigation of circulating levels of inflammatory cytokines, oxidative stress markers and iron regulatory and metabolic proteins in NBIA patients to include a group of patients with PKAN. Methods: Plasma samples from 15 PKAN patients were collected at the UCSF Benioff Children's Hospital in Oakland, California. Similarly, a plasma sample from a patient with PLAN was collected in Campbell River, British Columbia. Plasma samples from a matched group of 15 healthy controls were also collected at the University of Victoria. All patients provided informed consent to the study. The pro-inflammatory cytokines IL-6 and TNFα as well as the anti-inflammatory cytokine IL-10 were measured by ELISA. Total levels of the lipid peroxidation product malondialdehyde (MDA) were measured using N-Methyl-Phenyl-Indole (NMPI). Free, acutely generated, MDA not bound to proteins, was measured by removing plasma proteins via a 10KD spin filtration then measuring the MDA content of resulting filtrate using NMPI. Results: The levels of MDA and Free MDA were significantly elevated in PKAN patients at baseline in comparison to controls (p = 0.05, p = 0.03). IL-6 and TNFα were slightly, but not significantly elevated at baseline compared to controls. We previously demonstrated, similar elevations of oxidative stress in our case study of an NBIA patient with PLAN1. Additionally, all three inflammatory cytokines measured for this study expansion in PLAN were higher than average levels observed in the PKAN and control groups (S ee Table 1). Further analysis of systemic biomarkers in NBIA including proteomic analysis of 30 systemic blood proteins, including iron trafficking proteins is ongoing. Conclusions: We expand previous findings of elevated levels of systemic oxidative stress in other neurodegenerative diseases such as PD to include NBIA patients with PKAN and PLAN. We provide novel evidence of elevated levels of Free MDA; representative of an acute oxidative stress burden in NBIA in addition to the previously noted elevation in total MDA levels. We provide preliminary signs that of an accompanying inflammatory burden in NBIA, but a larger sample group may be needed to determine its significance. References M. Minkley, A. Jackson, D. Smith, C. Borchers, E. Vichinsky, R. Nashmi, P.B. Walter and P. M. Macloed. (2017). Neurodegeneration with Brain Iron Accumulation: PLA2G6-Associated Dystonia-Parkinsonism: Clinical and Animal Studies. Presented at the 2017 European Human Genetics Conference, Copenhagen, Denmark . Disclosures Minkley: Apopharma: Research Funding. Neumayr: Apopharma: Research Funding. Walter: Apopharma: Research Funding.

Background: Marfan’s syndrome is an inherited disorder that affects the connective tissue. It has been proposed that mutations of FBN1 gene or of transforming growth factor (TGF)-beta type II receptor may be responsible for its pathogenesis. However, the role of TGF-beta signaling pathway in the development of Marfan’s syndrome has not been comprehensively investigated. Materials and methods: Surgical specimens of the aorta were obtained from two female Marfan patients, and the control aortic tissue was taken from an autopsy of a healthy individual. The aortic specimens were examined with hematoxylin-eosin, Masson’s trichrome, von Gieson/victoria blue-van Gieson bichrome, and immunohistochemical stainings of TGF-beta1, TGF-beta type I receptor, Smad2/3, Smad4 and Smad7. Results: Hematoxylin-eosin staining demonstrated severe elastic lamellar disruption and patchy vascular smooth muscle dissolution in the aortic media of the Marfan patients. Collagen deposition, interlamilar elastic fiber fragmentation, loss or proliferation, and acid mucopolysaccharide accumulation were observed in the disarrayed aortic wall structures of Marfan patients by Masson’s trichrome, victoria blue-van Gieson bichrome, and Alcian blue and periodic schiff’s (AB-PAS) stainings, respectively. By immunohistochemistry, structural disruptions with enhanced TGF-beta;1 in the cytoplasm, Smad2/3 in the interstices, Smad4 in the cytoplasm, nuclei or interstices, and OOO Smad7, in the nucleus along with attenuated TGF-beta type I receptor in the aortic tissues of Marfan patients in comparison to the healthy control. Conclusions: Marfan patients may have aberrant TGF-beta signaling pathway associated with increased collagen deposition, interlamilar elastic fiber degenerative changes, and acid mucopolysaccharide accumulation. The signaling dysregulation may play an important role in the pathogenesis of this genetic disorder.

Abstract Aim: Hemophilia A (HA) is caused by abnormalities in the Factor VIII gene. Certain abnormalities correlate with disease severity. Here, we report the genotype-phenotype correlation for all Victorian HA patients. Methods: Using the Australian Bleeding Disorders Registry, Victorian HA patients were identified. All genetic testing was conducted at Southern Health. The testing algorithm is summarized in Figure 1. Mutations were compared with the list of known Factor 8 mutations on the Champ and EAHAD F8 Variant Databases. A PubMed search was undertaken for any mutations not on either database. If this too was unrevealing, the mutation was designated novel. In-silico analysis was conducted on all novel mutations using three open-access, online prediction tools: a) Mutation Taster; b) Poly-Phen 2; c) Human Splice Site Predictor. Results: 318 patients with matched clinical and genetic records were identified. 275 had known FVIII mutations and 36 novel FVIII mutations were discovered. Eight patients (3%) had no mutations identified. (Table 1) In severe HA the intron-22 inversion was the most common mutation (47/122, 38%). Missense mutations predominated in mild and moderate HA. Inhibitors were present in 44/318 patients, the majority of whom had 26/44 (59%) severe HA. 20/36 novel mutations (55%) were associated with severe HA, 12/36 (33%) with mild HA and 4/36 (11%) with a moderate HA. Novel mutations associated with non-severe phenotypes were mostly missense mutations (15/16); More diversity was seen in the novel mutations causing a severe HA with a fairly even distribution of mutations: missense (7/20), nonsense (4/20) and small deletions and insertions (8/20). One large deletion involving a 6.5kb region of exon 26, as well as one duplication of exons 7 to 9 - was seen in the severe group. In-silico analysis predicted that all novel severe HA mutations were likely to be pathogenic.Inhibitors were seen in 7 patients with novel mutations. Of the 36 novel mutations we described, 9/36 (25%) were seen in other family members - often female carriers. All 9 mutations caused a severe phenotype which is not unexpected given that the screening and testing of family members would be unlikely to take place in patients who have a mild phenotype and rarely require supportive medical care Conclusion: This study adds 36 novel mutations to the currently known FVIII haemophilic mutations. It also confirms that the frequency and correlative clinical severity of known genetic mutations in the Victorian HA cohort is similar to that described internationally. Disclosures No relevant conflicts of interest to declare.

Much of the fascination that Petronius' Satyricon holds for its readers originates in the work's gleeful violation of traditional categories of classical genres. Critical terminology makes explicit the issue of unconventionality, as it is reduced to the neutral word ‘work’ in describing the Satyricon, which, as far as we can tell, belongs to no single category (e.g. novel, romance, satire), but appropriates elements from many sources in both poetry and prose. Perhaps if we had more evidence with which to compare the work, such as a greater selection of Menippean satire or proto-novels from antiquity, we might be able to identify it more accurately. But the suspicion remains that the intense variety of its evocations, allusions, and parodic passages differentiates it clearly from its component genres without allowing it to settle firmly in any one established genre. A certain amount of ‘Kreuzung der Gattungen’ is, of course, typical of both Alexandrian and consequently Roman texts. But the Satyricon seems to revel in its generic instability; it plays with the notion of ‘literariness’ by revealing impulses from non-literary forms such as mime and subliterary prose fiction, raising this material to an unfamiliar level of literary sophistication even as it debases other traditional genres (e.g. epic) through parodic techniques. One of the results of this open experimentation with style and decorum is an extremely dense fabric of literary (and sub-literary) allusion which some would label ‘literary opportunism’. The reader quickly learns to expect intertextual pyrotechnics, swift changes from the sublime to the ridiculous, and humorous incongruities in plot and form, as the stylistic disorder of the text reflects the topsyturvy Petronian world. The modern reader's response to this profusion of referents is to explore the recognizable categories and sources embedded in the work, to tease out the familiar elements in the hope of gaining a better understanding of the whole. Since a great deal of the allusion in the Satyricon functions parodically, there is yet another step necessary in the interpretation, namely taking into account the effect of the decontextualization of language and events from the source material and their recombination and transformation into the new text.

Background:Sleep is an essential aspect of health that is commonly disrupted in patients with axial spondyloarthritis (axSpA).Objectives:This analysis aims to assess the prevalence and associated factors of sleep disorders in a large sample of axSpA patients.Methods:In 2016, a sample of 680 unselected patients with axSpA participated in the Atlas of Axial Spondyloarthritis in Spain through an online survey. The sample was divided into: 1) Patients with sleep disorders and 2) Patients without sleep disorders. Disease activity through BASDAI (0-10), spinal stiffness (3-12), functional limitation (0-54) and, mental health through a 12-item General Health Questionnaire GHQ-12 (0-12) were assessed. The Mann-Whitney and Pearson’s chi-square tests were used to analyse possible relationships between independent sociodemographic characteristics, employment, lifestyle, patient-reported outcomes and comorbidity variables with sleep disorders. Univariate and multivariate binary logistic regression was used to determine the possible association of the independent variables on sleep disorders.Results:Mean age was 45.7 years, 52.5% female, 36.9% had a university degree, and 71.5% were married. The prevalence of sleep disorders was 19.7%. Those who reported sleep disorders presented higher disease activity (6.3 vs 5.4, p<0.001), worse mental health (7.7 vs 5.0, p<0.001), greater functional limitation (45.7 vs 41.4, p<0.001), greater spinal stiffness (8.0 vs 7.3, p=0.008), and longer diagnostic delay (10.5 vs 7.9, p=0.021). 29.9% of the patients on sick leave had sleep disorders, compared to only 15.4% of employees (p=0.013). In addition, 23.0% of those who were physically active had sleep disorders compared to only 7.1% of those not physically active (p<0.001). Sleep disorders were more prevalent in patients with other comorbidities such as anxiety (60.0% vs 9.7%, w/o anxiety, p<0.001) and depression (66.0% vs 11.7% w/o depression, p<0.001). In the multivariate binary logistic regression, depression (OR= 3.89), anxiety (OR= 3.84), and a longer diagnostic delay (B=0.034) remained significantly associated with sleep disorders. Excluding mental comorbidity parameters from the model, physical activity (OR= 3.52) and disease activity (B= 0.175) remained significantly associated with sleep disorders (Table 1).Table 1.Logistic regression to analyses factor associated with sleep disorders (N= 366)Univariate logistic analysisMultivariate logistic analysisMultivariate logistic analysis*ORp-value1ORp-value1ORp-value1Qualitative factorsEmployment. Sick leave1.9370.0031.5540.1801.5400.131Physical activity. Yes3.914<0.0012.4100.1963.5160.048Anxiety diagnosis13.925<0.0013.840<0.001----Depression diagnosis14.616<0.0013.886<0.001----Quantitative factorsBp-value2Bp-value2Bp-value2BASDAI (0-10)0.238<0.0010.0360.6730.1750.015GHQ-120.141<0.0010.0450.204----Functional Limitation (0-54)0.049<0.001-0.0110.5600.0220.166Spinal Stiffness (3-12)0.1040.0080.0160.7750.0200.683Diagnostic Delay0.0410.0010.0340.0440.0250.083*Excluding mental health factors. 1p-value for test H0: OR = 1 2p-value for test H0: B = 0Conclusion:One of five patients with axSpA reported sleep disorders. The presence of mental comorbidities such as anxiety and depression increases the likelihood of sleep disorders. Moreover, physical activity and disease activity also seem to increase the probability on sleep disorders. Referral to mental health specialists together with optimal healthcare management should be key for the reduction of sleep disorders in axSpA.Acknowledgements:This study was supported by Novartis Spain. The authors would like to thank all patients who participated in this study.Disclosure of Interests:Marco Garrido-Cumbrera: None declared, Victoria Navarro-Compán Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Eduardo Collantes-Estevez Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Pedro Zarco-Montejo: None declared, Sergio Sanz-Gómez: None declared, Carlos Sastré Employee of: Novartis Farmacéutica Spain, Pedro Plazuelo-Ramos: None declared, Jordi Gratacos-Masmitja Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB.

157 Background: Pediatric brain tumor survivors (PBTS) often experience late effects in social functioning that mirror those seen in children with autism spectrum disorder (ASD). This study evaluated group differences in facial processing abilities and social functioning between school-aged PBTS, children with ASD, and typically developing children (TDC). Methods: PBTS(n=40;65% male; mean age=13.9 years; mean age at diagnosis=5.8 years)were at least 5 years from tumor diagnosis,2 years from end of tumor-directed therapy and absent a multi-system genetic disorder or developmental delay before tumor diagnosis. Participants completed measures of IQ, facial affect/identity recognition(Victoria/Yale Face Processing Battery), and social functioning(Children’s Communication Checklist-2, Vineland Adaptive Behavior Scales,2nd Ed. and Social Responsiveness Scale, 2nd Ed.).PBTS data were compared to a previously collected sample of age, gender, and IQ-matched children with ASD(n=41)and TDC (n=39).One-way ANOVA evaluated differences between groups with Tukey post-hoc tests.Results: IQ for PBTS(m=100.9; SD=16.27),ASD(m=100.17; SD=17.09),and TDC(m=104.72; SD=14.0)were all in the average range.One-way ANOVA revealed group differences for facial identity recognition[ F (2,114)=4.8 η²=.09 , p=.01],facial affect recognition[ F (2, 114)=3.8 , η²=.07, p=.024],and all social functioning measures[ p=.000].Tukey tests revealed PBTS facial affect recognition to be significantly worse than TDC(p < .05)and more comparable to youth with ASD for both facial affect and identity recognition.PBTS also showed worse social functioning than TDC and better than ASD youth across social measures( p’s < .01).Conclusions: Findings suggest PBTS demonstrate impairments in facial affect and identity recognition and social functioning compared to TDC.PBTS facial processing abilities appear similar to those of youth with ASD.PBTS may benefit from multi-disciplinary interventions similar to those used in ASD to improve social functioning. Screening facial processing abilities may identify those at higher risk for social functioning deficits.

Background:Sleep is an essential health aspect that is often impacted in patients with axial spondyloarthritis (axSpA).Objectives:This analysis aims to assess the prevalence and associated factors of sleep disorders in a large sample of European axSpA patients.Methods:Data were analyzed from 2,846 unselected patients with self-reported clinician-given diagnosis of axSpA of the European Map of Axial Spondyloarthritis (EMAS) through an online survey (2017-2018) across 13 European countries. Socio-demographic data; BASDAI [0-10] scores; engagement in physical activity; axSpA influence on work choice (assessed with yes/no question “Was your current or past work choice in any way determined by axSpA?”); risk of psychological distress (12-item General Health Questionnaire [GHQ-12; 0-12]); functional limitation [0-54] and self-reported anxiety and depression were evaluated. Presence of sleep disorders was assessed by the question: “Please indicate whether you have been diagnosed with any of the following: sleep disorders”. A Mann-Whitney test was used to compare the means of numerical variables between dichotomous variables, the Chi-Square test was used to compare the distribution between the categorical variables. Simple and multivariable logistic regression models were used to identify associations between sleep disorders and disease characteristics, mental health and work-related variables.Results:Age of respondents was 43.9 years; 61.3% were female; 48.1% had a university degree; 67.9% were married and 71.3% were HLA-B27 positive. The prevalence of sleep disorders was 39.0%. In the bivariate analysis, presence of sleep disorders was associated with female gender (68.3% vs. 31.7%; p<0.001); overweight/obese (56.5% vs. 49.8%; p<0.001); increased BASDAI scores (6.1±1.8 vs. 5.0±2.1; p<0.001); fatigue (7.0±2.0 vs. 5.8±2.4; p<0.001); morning stiffness (5.8±2.4 vs. 4.8±2.4; p<0.001), work impact (56.5% vs. 38.2%; p< 0.001); anxiety (56.8% vs. 12.5%; p<0.001); depression (51.8% vs. 10.1%; p<0.001) and higher GHQ-12 scores (6.4±4.0 vs. 3.9±3.9; p<0.001). However, factors that remained independently associated with sleep disorders in the multivariable analysis were anxiety (OR=3.8 p<0.001) and depression (OR=3.1 p<0.001) and female gender (OR=1.4; p=0.002) [Table 1].Table 1.Regression analysis to predict presence of sleep disorders (N=2191)Simple logistic regressionMultivariable logistic regressionOR95% CIp-valueOR95% CIp-valueGender (female)1.591.36-1.87<0.0011.401.13-1.730.002Marital status (married)1.130.99-1.280.074NANANAOverweight/Obesity1.311.12-1.530.0011.391.14-1.710.001BASDAI (0-10)1.331.27-1.39<0.0011.070.95-1.210.246Fatigue/Tiredness (0-10)*1.281.23-1.33<0.0011.040.97-1.120.271Morning Stiffness intensity (0-10)*1.191.15-1.23<0.0011.050.98-1.130.188Reported Work impact (yes)2.101.78-2.48<0.0011.291.05-1.580.015Anxiety (yes)9.187.58-11.11<0.0013.842.99-4.94<0.001Depression (yes)9.537.78-11.66<0.0013.092.37-4.02<0.001GHQ-12 (0-12)**1.161.14-1.19<0.0011.031.00-1.060.029*As measured by the respective item of the BASDAI scale.**12-item General Health Questionnaire. A value of 3 or above indicates a risk of poor mental health.Conclusion:Sleep disorders were highly prevalent among axSpA European patients and strongly associated with female gender and reporting worse mental health, and spinal stiffness. Patients on permanent and temporary sick leave were more likely to report sleep disorders. The strong association between sleep disorders with both anxiety and depression should encourage rheumatologists to screen their patients with sleep disturbance in case they require additional specialist support.Acknowledgements:This study was supported by Novartis Pharma AG. The authors would like to thank all patients who participated in the study.Disclosure of Interests:Marco Garrido-Cumbrera: None declared, Victoria Navarro-Compán Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB., Laura Christen Employee of: Novartis Pharma AG, Christine Bundy Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, and Pfizer, Raj Mahapatra: None declared, Souzi Makri: None declared, Carlos Jesús Delgado-Domínguez: None declared, José Correa-Fernández: None declared, Denis Poddubnyy Speakers bureau: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Abbvie, MSD, Novartis, and Pfizer.

Background:Pain is a hallmark of axial spondyloarthritis (axSpA) and can significantly deteriorate patients’ health status.Objectives:This analysis aims to investigate factors associated with pain intensity in a large sample of European axSpA patients.Methods:2,846 unselected patients participated in EMAS, a cross-sectional study (2017-2018) across 13 European countries. Data from 2,636 participants who reported pain were analysed. Pain was measured by the mean of two BASDAI questions (range 0 “no pain” to 10 “most severe pain”): “How would you describe the overall level of AS neck, back or hip pain you have had?” and “How would you describe the overall level of pain/swelling in joints other than neck, back, hips you have had?”. Linear regression analysis was applied to identify associations between pain intensity and sociodemographic factors, patient-reported outcomes [BASDAI (0-10), spinal stiffness (3-12), functional limitation (0-54), mental health using the 12-item General Health Questionnaire GHQ-12 (0-12)], work life, physical activity and comorbidities, for which 850 patients were included.Results:The mean age of the sample was 44 years, 61.4% were female, 49.4% had a university degree and 67.7% were married. The average reported pain intensity was 5.3 (±2.2); 76.2% reported pain intensity ≥4, with the greatest intensity reported by women (5.5 vs 4.9, p<0.001), those not university educated (5.6 vs 5.0, p<0.001), separated or divorced compared to singles (5.8 vs 5.2, p=0.004), and not physically active (5.7 vs 5.2, p<0.001). In addition, employed patients who experienced work-related issues reported greater pain (5.2 vs 3.9) as did those who experienced/ believed they would face difficulties finding work due to axSpA (5.9 vs 4.3), and those whose employment choice was determined by axSpA (5.7 vs 4.9; all p<0.001). Moreover, associations with anxiety (5.9 vs 5.0), depression (6.1 vs 5.0) and sleep disorders (5.9 vs 4.9; all p<0.001) were also found. The multiple linear regression model showed that those with higher pain intensity reported at least one work-related issue (B=0.65), difficulties finding work due to axSpA (B=0.48), not having attended university (B=0.38), greater spinal stiffness (B= 0.29), being female (B=0.26) and poorer mental health (GHQ-12) (B=0.10) (Table 1).Table 1.Regression analysis of the variables associated with pain intensity (0-10 NRS), n=850UnivariableMultivariableB95% CIB95% CIGender. Female10.6040.432, 0.7750.2600.003, 0.517Educational level. No University20.6710.504, 0.8380.3760.118,0.634Marital Status. Divorced/Separated30.4950.209, 0.780-0.044-0.468, 0.380Body Mass Index. Obese40.362-0.097, 0.821NANAGHQ-12 (0-12)0.1820.163, 0.2010.1000.064, 0.137Functional Limitation (0-54)0.0360.030, 0.0410.009-0.001, 0.018Spinal Stiffness (3-12)0.3570.326, 0.3880.2880.234, 0.342Diagnostic Delay, years0.0200.010, 0.030-0.015-0.032, 0.002Work-Related Issues. Yes1.3381.095, 1.5820.6540.338, 0.970Difficulty finding job due to axSpA. Yes1.5681.362, 1.7740.4760.176, 0.776Work choice determinate by axSpA. Yes0.8080.633, 0.9830.199-0.069, 0.467Physical activity. No0.4940.263, 0.725-0.128-0.497, 0.242Anxiety diagnosis. Yes0.9350.753, 1.117-0.047-0.416, 0.321Depression diagnosis. Yes1.1070.919, 1.2950.115-0.270, 0.500Sleep disorder diagnosis. Yes1.0420.871, 1.213-0.091-0.392, 0.2111Female vs Male; 2No university studies (no schooling, primary and high school) vs University studies; 3Divorced/separated vs single, married and widow; 4Obese vs not obese (underweight, normal and overweight).Conclusion:Pain was most strongly associated with working life impairment, as well as with spinal stiffness. Pain was also associated with suffering from depression, anxiety and sleep disorders. Understanding how pain affects individuals and shared-decision making between rheumatologists and patients are essential for long-term disease management and preserving quality of life of axSpA patients.Acknowledgements:This study was supported by Novartis Pharma AG. The authors would like to thank all patients who participated in the EMAS study.Disclosure of Interests:Marco Garrido-Cumbrera: None declared, Victoria Navarro-Compán Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Christine Bundy Consultant of: Abbvie, Celgene, Janssen, Lilly, Novartis, and Pfizer, Laura Christen Employee of: Novartis Pharma AG, Raj Mahapatra: None declared, Souzi Makri: None declared, Carlos Jesús Delgado-Domínguez: None declared, José Correa-Fernández: None declared, Pedro Plazuelo-Ramos: None declared, Denis Poddubnyy Consultant of: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Abbvie, MSD, Novartis, and Pfizer.

Background:Axial spondyloarthritis (axSpA) is associated with a high burden of disease, which may lead to inability to work and disability.Objectives:This analysis aims to identify factors associated with inability to work and disability among European axSpA patients.Methods:Data from 2,846 unselected patients participating in EMAS, a cross-sectional study (2017-2018) across 13 European countries were analysed. The sample was divided into those on permanent sick leave or with a recognised disability (Group 1) and those with neither permanent sick leave nor a recognized disability (Group 2). Mann-Whitney and Pearson’s χ2 tests were used to analyse possible differences between groups regarding sociodemographic characteristics, patient-reported outcomes [BASDAI (0-10), GHQ-12 (0-12), functional limitation (0-54) and spinal stiffness (3-12)], lifestyle habits, working life, and comorbidities). Univariable and multivariable binary logistic regression were used to analyse variables possibly explaining being on permanent sick leave and disability, for which 1,657 patients were included.Results:Mean age was 43.9 years, 61.3% were female, 48.1% had a university degree, and 67.9% were married. Patients in Group 1 (34.4%; n=978) were more likely to be women (54.3%), married (71.1%), with higher disease activity (BASDAI 5.9 vs. 5.3), functional limitation (25.1 vs. 18.0), spinal stiffness (8.6 vs. 7.3; all p<0.001), and longer diagnostic delay (8.1 vs 7.1 years; p = 0.01) than those in Group 2 (65.6%; n=1,868). In addition, 88.0% of Group 1 (n=728) had difficulties in finding a job due to axSpA throughout life; and more than 30.0% reported a diagnosis of anxiety, depression, or sleep disorders. Moreover, being in Group 1 was associated with higher functional limitation in all daily activities. In the multivariable binary logistic regression, the qualitative variables associated with permanent sick leave or disability were: difficulties finding work (OR= 2.52), belonging to a patient organisation (OR= 1.54) and work choice determined by axSpA (OR= 1.38). The quantitative variables associated with permanent sick leave or disability were: higher spinal stiffness (OR= 1.09), older age (OR= 1.03), longer disease duration (OR= 1.03), shorter diagnostic delay (OR= 0.98), and higher functional limitation (OR= 1.01) (Table 1).Table 1.Regression analysis for variables explaining being on permanent sick leave or disability (n=1,657)Univariable logistic analysisMultivariable logistic analysisQualitative variablesOR95% CI3OR95% CI3Gender11.571.34, 1.831.240.97, 1.57Educational level21.711.46, 2.001.080.86, 1.35Member of a patient organisation. Yes1.961.67, 2.291.541.23, 1.94Smoking. Yes1.281.08, 1.511.220.96, 1.55Difficulty finding job due to axSpA. Yes3.712.89, 4.772.521.83, 3.47Work choice determined by axSpA. Yes1.691.43, 1.991.381.09, 1.75Anxiety diagnosis. Yes1.271.07, 1.510.980.72, 1.34Depression diagnosis. Yes1.581.33, 1.891.250.92, 1.69Sleep disorder diagnosis. Yes1.331.13, 1.560.950.73, 1.23Quantitative variablesOR95% CI3OR95% CI3Age. Years1.041.03, 1.041.031.01, 1.04BASDAI (0-10)1.181.13, 1.241.060.98, 1.13Functional limitation (0-54)1.031.02, 1.031.011.00, 1.02Spinal stiffness (3-12)1.251.20, 1.291.091.03, 1.15Diagnostic delay1.011.01, 1.020.980.96, 0.99Disease duration1.041.03, 1.051.031.01, 1.041Male vs Female; 2No university studies vs university studies. 395% CI for test H0: OR=1Conclusion:One third of patients reported being on permanent sick leave or having a recognised disability. They were more likely to have higher spinal stiffness scores, were older in age, experiencing difficulty finding a job, and belonged to a patient organisation. Increased efforts in relation to early access to effective treatments and the creation of flexible working environments are essential for axSpA patients to continue working and remain active, which benefits their quality of life.Acknowledgements:This study was supported by Novartis Pharma AG.The authors would like to thank all patients who participated in this study.Disclosure of Interests:Marco Garrido-Cumbrera: None declared, Christine Bundy Consultant of: Abbvie, Celgene, Janssen, Lilly, Novartis, and Pfizer, Victoria Navarro-Compán Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Laura Christen Employee of: Novartis Pharma AG, Raj Mahapatra: None declared, Souzi Makri: None declared, Carlos Jesús Delgado-Domínguez: None declared, David Gálvez-Ruiz: None declared, Pedro Plazuelo-Ramos: None declared, Denis Poddubnyy Consultant of: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Abbvie, MSD, Novartis, and Pfizer.

Background:Axial Spondyloarthritis (axSpA) can impact patients’ sexual life.Objectives:The aim is to assess the prevalence of functional limitation in sexual activity in axSpA patients in Spain and its associated factors.Methods:Data from an online survey of 680 unselected axSpA patients pertaining to the Atlas of Axial Spondyloarthritis in Spain were collected. Functional limitation in intimate relations was assessed through a 3-point Likert scale (low, medium, and high) and the sample was divided into 1) low-medium and 2) high. Mann-Whitney and χ2 tests were used to analyse relations between sociodemographic, employment, lifestyle, patient-reported outcomes, and comorbidities with respect to functional limitation in intimate relations. Univariate and multivariate binary logistic regression was used to analyse its associated factors.Results:605 axSpA patients were included: the mean age was 45.5 years, 51.4% were female, 38.3% had a university degree, and 70.7% were married. A total of 57.7%, 28.9%, and 13.4% participants presented high, medium, and low limitation in intimate relations, respectively. Patient with high functional limitation in intimate relations were younger (44.6 vs 46.7, p=0.032), female (67.2% vs 47.6% of male, p<0.001), did not belong to a patient organisation (62.7% vs 51.5% of members, p=0.006), were on sick leave (73.3% vs 51.9% of employed, p<0.001) and smoked more (67.3% vs 52.6%, p<0.001). The high limitation group presented higher disease activity (6.3 vs 4.9), functional limitation (48.2 vs 34.4) and spinal stiffness (7.9 vs 6.9, all p<0.001), worse mental health (7.0 vs 4.1, p<0.001), longer diagnostic delay (9.2 vs 7.6, p=0.019), and more comorbidities such as anxiety (73.3% vs 53.2%), depression (80.0% vs 53.3%) and sleep disorders (70.9% vs 53.9%, all p<0.001). In addition, 80.3% of patients with decreased frequency of intimate relations presented high functional limitation in intimate relations (vs 10.0% with more frequency) and 81.4% had experienced a worsening relationship with their spouse (vs 55.6% with better relation, all p<0.001). In the multivariate binary logistic regression, the qualitative factors associated with high functional limitation in intimate relations were a reduction in the frequency of intimate relations (OR= 18.66) and smoking (OR= 2.89), while the quantitative factor associated with high functional limitation in the intimate relation was higher overall functional limitation (B= 0.292; Table 1).Table 1.Logistic regression to analyse factor associated with high functional limitation in intimate relation (N= 302)Univariate logistic analysisMultivariate logistic analysisORp-value1ORp-value1Qualitative factorsGender. Female2.254<0.0011.3110.569Patient Organization. Member0.6320.0060.5150.171Employment. Sick leave2.354<0.0011.0600.910Smoking. Yes1.8520.0012.8850.020Anxiety diagnosis. Yes2.420<0.0010.5690.306Depression diagnosis. Yes3.509<0.0011.6650.408Sleep disorder diagnosis. Yes2.0810.0010.6250.381Frequency of intimate relation. Less than before vs same or more than before12.605<0.00118.655<0.001Relation with spouse. Worse than before5.480<0.0011.2560.636Quantitative factorsBp-value2Bp-value2Age-0.0180.0210.0100.718BASDAI (0-10)0.398<0.001-0.1550.284GHQ-12 (0-12)0.154<0.0010.0030.952Functional Limitation (0-54)0.237<0.0010.292<0.001Spinal Stiffness (3-12)0.131<0.001-0.1160.226Diagnostic Delay0.0300.0130.0200.4741p-value for test H0: OR = 1 2p-value for test H0: B = 0Conclusion:More than half of patients with axSpA in Spain presented high functional limitation in intimate relations, who more likely presented decreased frequency of relations. This may indicate that avoidance of sexual encounters is a common coping mechanism for the functional limitation accompanying this disease. Healthcare providers can play a key role in the sexual health of axSpA patients by improving patient-physician communication and raising awareness about the benefits of counselling on a healthy sexual life.Acknowledgements:This study was supported by Novartis Spain. The authors would like to thank all patients who participated in this study.Disclosure of Interests:Marco Garrido-Cumbrera: None declared, Jordi Gratacos-Masmitja Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Eduardo Collantes-Estevez Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Pedro Zarco-Montejo: None declared, Carlos Sastré Employee of: Novartis Farmacéutica Spain, Sergio Sanz-Gómez: None declared, Pedro Plazuelo-Ramos: None declared, Victoria Navarro-Compán Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB.